The neurocognitive benefits of proton beam therapy for patients with oligodendroglioma

Trial ID: ISRCTN13390479

Other - Phase 3 - Recruiting

Background and study aims The study is called the APPROACH study. APPROACH stands for Analysis of Proton versus Photon Radiotherapy in Oligodendroglioma & Assessment of Cognitive Health. Oligodendroglioma is an uncommon brain tumour with an excellent outlook. Standard treatment involves surgery to remove as much tumour as possible, radiotherapy (RT) and then chemotherapy. RT helps stop the tumour from re-growing. Standard RT for adult patients in the UK uses photon RT. Photon RT is given as lots of small treatments on weekdays over about six weeks. This is the best way to control the tumour whilst minimising side effects in normal brain tissue. Unfortunately, photon RT for oligodendroglioma can cause long-term side effects. These can develop years after RT and can include memory problems and difficulties in processing information. These can have a negative impact on quality of life. Proton beam radiotherapy (PBT) is an advanced type of RT, also given on weekdays over about six weeks. It requires expensive technology but can reduce the dose of RT delivered to the normal brain, including parts of the brain used for memory and information processing. We do not know, however, if these lower doses result in fewer long-term side-effects. We do not expect any difference in controlling the growth of the tumour as the same dose of RT is given to the tumour whether photon RT or PBT is used. To do this we will compare the long-term side effects of photon RT or PBT for patients with oligodendroglioma. We want to find out which is the best treatment for patients with oligodendroglioma to reduce long-term side effects. Who can participate? Patients with oligodendroglioma from across the UK What does the study involve? Participants in our study will be randomly assigned (by computer) to receive photon RT or PBT, with an equal chance of either. We will gather information on long-term brain function, quality of life, other side effects and tumour control. As part of the study we will look at whether travelling to a distant RT centre is acceptable to patients. Patients receiving photon RT will have this at their local RT centre. PBT is only available in Manchester and London, so patients having PBT will need to stay in Manchester or London for the treatment period (accommodation is provided). To assess long-term side effects, we will monitor patients for five years after RT. This will involve: - Carrying out short practical tasks and memory assessments to measure brain function - Completing questionnaires about quality of life and work - Having Magnetic Resonance Imaging (MRI) scans to monitor the tumour - Having blood tests to track hormone levels- these can also be affected by RT We will also ask carers to complete questionnaires, to assess carer experiences. What are the possible benefits and risks of participating?: By taking part in this study, the researchers hope to understand better the effects of lower dose of RT delivered to healthy brain, if side effects can be reduced and how it may impact a patient's quality of life. This will help hospitals in choosing the best treatment for future patients diagnosed with oligodendroglioma. Participants have a risk of side effects in both the radiotherapy groups. Because RT is given over several weeks it can disrupt to day-to-day life for patients and carers, especially as this condition often involves people of working age who are not allowed to drive due to their diagnosis. Possible side effects of chemotherapy are tiredness, nausea, vomiting, taste changes, sore mouth or mouth ulcer, infections, bruising and bleeding, poor appetite, diarrhoea, constipation, abdominal pain, anaemia, skin changes and allergic reactions. Possible side effects from radiotherapy could include; tiredness, patchy hair loss, headaches, dizziness, swelling in the brain, nausea, vomiting, skin redness or irritation on the scalp, weakness, seizures and dry mouth or taste changes. Patient and Public Involvement (PPI) has played a key role in the study: patients and carers supported the research question and follow-up plan and advised on study design. At least three PPI representatives will sit on the Trial Management Group to ensure the patient voice is represented. The PPI group will have an active role throughout and will contribute to the final scientific report and in the dissemination of the findings, that will be shared with trial participants and the wider public. Where is the study run from? University of Leeds (UK) When is the study starting and how long is it expected to run for? January 2024 to July 2032 Who is funding the study? National Institute for Health and Care Research - Efficacy and Mechanism Evaluation Programme (NIHR) (UK) Who is the main contact? Dr Samantha Noutch, approach@leeds.ac.uk (UK) https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-proton-beam-therapy-for-people-with-a-brain-tumour-called-oligodendroglioma

Conditions

• Brain cancer, oligodendroglioma
• Cancer

Interventions

• Photon radiotherapy (RT), proton beam therapy (PBT)

Eligibility

Inclusion criteria

• 1. Histologically proven diagnosis of oligodendroglioma (ODG) with 1p19q co-deletion and isocitrate dehydrogenase (IDH) mutation 2. Randomisation must be performed within 28 days of the magnetic resonance imaging (MRI) that leads to the decision that radiotherapy (RT) is required at that point in time. Outside of 28 days, an updated MRI is required to serve as a contemporaneous baseline scan to assess response to further treatment. 3. Karnofsky Performance Status (KPS) ≥70%. 4. Adequate wound healing and recovery if recent surgery. 5. Suitable to complete baseline neurocognitive testing (No access to translated tests, can only be administered in English). 6. Patients of childbearing potential should be asked to confirm that they are not pregnant to confirm trial eligibility. Formal Pregnancy testing should be performed if there is any doubt as to pregnancy status or if felt appropriate, including in circumstances such as irregular periods, unprotected sexual intercourse since the last menstrual period, missed contraceptive pill or antibiotics during the last menstrual cycle or failure of barrier contraception. 7. Fertile participants, born male, must agree to practice methods of contraception that are considered medically acceptable for the duration of RT, adjuvant chemotherapy and for 6 months post-end of treatment if sexually active with a person of child-bearing potential. 8. Able to swallow oral medication. 9. Able to provide study-specific informed consent. 10. Age 25 or above at the point of starting RT treatment. 11. No known haematological, renal or hepatic impairments making PCV chemotherapy inappropriate

Exclusion criteria

• 1. Pregnancy (positive pregnancy test) or lactating. 2. Prior cranial or head and neck radiotherapy (RT). 3. Any previous chemotherapy for the treatment of oligodendroglioma (ODG). 4. Comorbid neurodegenerative diseases that influence neurocognitive function (NCF). 5. Severe active co-morbidity making patient unsuitable for RT and/ or adjuvant chemotherapy (e.g., uncontrolled diabetes, uncontrolled hypertension). 6. Leptomeningeal disease. 7. Spinal or infratentorial disease. 8. Another currently active malignancy or another malignancy within the last 3 years. 9. Any contra-indication to procarbazine, vincristine or lomustine including: coeliac disease; the rare hereditary problems of galactose intolerance, total lactase deficiency or glucosegalactose malabsorption. 10. Any recognised genetic syndrome causing sensitivity to radiotherapy. 11. Patient unwilling/ unable to attend for follow up in the local radiotherapy centre. 12. Contraindication to MRI or gadolinium.

Sponsor

University of Leeds

Source: https://www.isrctn.com/

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